A5007143711- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Spectroscopy and Quantum Chemical Studies
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Bacteriophages and microbial interactions
- Fungal and yeast genetics research
- Lipid Membrane Structure and Behavior
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Microtubule and mitosis dynamics
- Racial and Ethnic Identity Research
- Nuclear materials and radiation effects
- Viral Infectious Diseases and Gene Expression in Insects
- Medical Education and Admissions
- Peanut Plant Research Studies
- RNA and protein synthesis mechanisms
- Molecular Spectroscopy and Structure
- Health and Well-being Studies
- Biosimilars and Bioanalytical Methods
- Connective tissue disorders research
- Spectroscopy Techniques in Biomedical and Chemical Research
- Advanced Fluorescence Microscopy Techniques
Harvard University
2020-2024
Boston VA Research Institute
2020-2024
University of Pennsylvania
2017
University of Mississippi Medical Center
2012-2017
University of California, Berkeley
2016
University of Maine
2009-2015
Russell Sage College
2008
A dynamic viral spike Efforts to protect human cells against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the trimeric (S) protein. Several structures shown a stabilized ectodomain of in its prefusion conformation. Cai et al. now provide insight into structural changes S protein that result fusion and host cell membranes. They purified full-length determined cryo–electron microscopy both postfusion conformations. These add our understanding function could...
Substitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. The G614 strain and its recent variants are now dominant circulating forms. Here, we report cryo-electron microscopy structures a full-length S trimer, which adopts three distinct prefusion conformations that differ primarily one receptor-binding domain. A loop disordered D614 trimer wedges between...
SARS-CoV-2 from alpha to epsilon As battles contain the COVID-19 pandemic continue, attention is focused on emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that have been deemed concern because they are resistant antibodies elicited by infection or vaccination increase transmissibility disease severity. Three papers used functional and structural studies explore how mutations in viral spike protein affect its ability infect host cells evade immunity....
Abstract The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. spike (S) protein of virus forms a trimer and catalyzes fusion between viral target cell membranes - first key step infection. Here we report two cryo-EM structures, both derived from single preparation full-length S protein, representing prefusion (3.1Å resolution) postfusion (3.3Å conformations, respectively. spontaneous...
Septin complexes display remarkable plasticity in subunit composition, yet how a new assembled into higher-order structures confers different functions is not fully understood. Here, this question addressed budding yeast, where during meiosis Spr3 and Spr28 replace the mitotic septin subunits Cdc12 Cdc11 (and Shs1), respectively. In vitro, sole stable complex that contains both meiosis-specific septins linear Spr28–Spr3–Cdc3–Cdc10–Cdc10–Cdc3–Spr3–Spr28 hetero-octamer. Only coexpressed...
Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent ongoing pandemic, appears to facilitate rapid viral spread. The G614 variant has now replaced D614-carrying virus as dominant circulating strain. We report here cryo-EM structures a full-length S trimer carrying G614, which adopts three distinct prefusion conformations differing primarily one receptor-binding domain (RBD). A loop...
Class I methanol masers appear to probe very early stages of star formation. An observational survey the 44 and 36 GHz lines toward several star-forming regions was conducted using Haystack Observatory 37 m telescope. Examining intensities maser line as compared line, it is seen that enhanced sources where there no apparent sign Sources emission absent, but strong, be those ultracompact H ii millimeter continuum are present. Existing models for excitation show strong temperature density...
Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These are independent the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 2, exported as a result direct translocation through cell membrane. This process requires specific interactions with membrane phospholipids. In this review written by biologist, structural biologist two engineers, we discuss following subjects:...
Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains that continue to fuel COVID-19 pandemic despite intensive vaccination efforts throughout world. We report here cryo-EM structures full-length spike (S) trimers B.1.1.7 and B.1.351 variants, as well their biochemical antigenic properties. Mutations in protein increase accessibility its receptor binding domain also affinity for angiotensin-converting...
Passage through the eukaryotic cell cycle requires processes that are tightly regulated both spatially and temporally. Surveillance mechanisms (checkpoints) exert quality control impose order on timing organization of downstream events by impeding progression until necessary components available undamaged have acted in proper sequence. In budding yeast, a checkpoint exists does not allow timely execution G2/M transition unless collar septin filaments has properly assembled at bud neck, which...
Understanding surface and interfacial lateral organization in material biological systems is critical nearly every field of science. The continued development tools techniques viable for elucidation information therefore necessary to address new questions further current investigations. Sum frequency spectroscopy (SFS) a label-free, nonlinear optical technique with inherent specificity that can yield organizational on species. Unfortunately, SFS provides no spatial surface; small scale...
Model cellular membranes enable the study of biological processes in a controlled environment and reduce traditional challenges associated with live or fixed cell studies. However, model membrane systems based on air/water oil/solution interface do not allow for incorporation transmembrane proteins protein transport mechanisms. Conversely, phospholipid bilayer deposited via Langmuir–Blodgett/Langmuir–Schaefer method hydrogel layer is potentially an effective mimic cross section facilitates...
Septins are a protein family found in all eukaryotes (except higher plants) that have roles membrane remodeling and formation of diffusion barriers as scaffold to recruit other proteins. In budding yeast, proper execution cytokinesis cell division requires the collar circumferential filaments at bud neck. These assembled from apolar septin hetero-octamers. Currently, little is known about mechanisms control arrangement dynamics structures. this study, we utilized both Förster resonance...
The Harvard Cryo-Electron Microscopy Center for Structural Biology, which was formed as a consortium between Medical School, Boston Children's Hospital, Dana-Farber Cancer Institute, and Massachusetts General serves both academic commercial users in the greater community. facility strives to optimize research productivity while training become expert electron microscopists. These two tasks may be at odds require careful balance keep projects moving forward still allowing trainees develop...
Abstract G protein-coupled receptors (GPCRs) are key regulators of human physiology and the targets many small molecule research compounds therapeutic drugs. While most these ligands bind to their target GPCR with high affinity, selectivity is often limited at receptor, tissue, cellular level. Antibodies have potential address limitations but properties as remain poorly characterized. Here, using protein engineering, pharmacological assays, structural studies, we develop maternally selective...
A recent iteration of fluorescence correlation spectroscopy (FCS), z-scan FCS, has drawn attention for its elegant solution to the problem quantitative sample positioning when investigating two-dimensional systems while simultaneously providing an excellent method extracting calibration-free diffusion coefficients. Unfortunately, measurement planar using (FCS and) FCS still requires extremely mechanically stable positioning, relative a microscope objective. As axial position serves as...
The 2019 peanut crop was the worst year in recent history for aflatoxin contamination finished lots of shelled runner peanuts. This largely due to excessive heat and late season drought southeastern US. industry estimated that approximately 30% failed meet USDA specifications edible peanuts causing increased costs re-milling, material loss, diversion low value markets such as crushing oil. As a result, formed Aflatoxin Working Group at 2020 American Peanut Council’s Winter Conference (1)...